The primary interest of this laboratory is mammalian development and oncogenesis using both knockouts and transgenic animal model systems. Studies have being carried out on functions of fibroblast growth factor receptors (FGFRs) in mammalian development. FGFRs constitute a family of four membrane-spanning tyrosine kinases (FGFR1-4) which serve as high affinity receptors for at least nine growth factors (FGF1-9). FGFs/FGFRs signals may have many important biological functions, including developmental induction and differentiation, wound healing, tumor angiogenesis, cell growth and migration, as well as neuronal differentiation and survival. Moreover, it has been recently demonstrated that alterations in FGFRs are responsible for at least seven human inherited diseases. All of these are caused by single amino functions of FGFs!FGFRs signals in development and to gain insight into mechanism(s) underlying these inherited diseases, mice have been created that carry targeted disruption of each individual receptor through homologous recombination in ES cells. Analyses of these mutant mice revealed each of the FGF receptor to have distinct functions during murine development: FGFR-1 plays a role in axial organization during gastrulation; FGFR-2 plays a role at postgastrulation stages; FGFR-3 is a negative regulator in bone growth and development; and both FGFR-3 and FGFR-4 work together to monitor postnatal growth.